Advancements in materials science and fabrication techniques have contributed to the significant growing attention to a wide variety of sensors for digital healthcare. While the progress in this area is tremendously impressive, few wearable sensors with the capability of real-time blood pressure monitoring are approved for clinical use. One of the key obstacles in the further development of wearable sensors for medical applications is the lack of comprehensive technical evaluation of sensor materials against the expected clinical performance. Here, we present an extensive review and critical analysis of various materials applied in the design and fabrication of wearable sensors. In our unique transdisciplinary approach, we studied the fundamentals of blood pressure and examined its measuring modalities while focusing on their clinical use and sensing principles to identify material functionalities. Then, we carefully reviewed various categories of functional materials utilized in sensor building blocks allowing for comparative analysis of the performance of a wide range of materials throughout the sensor operational-life cycle. Not only this provides essential data to enhance the materials’ properties and optimize their performance, but also, it highlights new perspectives and provides suggestions to develop the next generation pressure sensors for clinical use.